Last update 01 Nov 2024

TOB2

Last update 01 Nov 2024

Basic Info

Synonyms

APRO5, bK223H9, KIAA1663

+ [8]

Introduction

Anti-proliferative protein inhibits cell cycle progression from the G0/G1 to S phases.

Drugs associated with TOB2

S115

Target

TOB2 x ubiquitin

Mechanism

TOB2 agonists [+2]

Active Org.

Shanghai Jiao Tong University

Originator Org.

Shanghai Jiao Tong University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TOB2

100 Translational Medicine associated with TOB2

0 Patents (Medical) associated with TOB2

188

Literatures (Medical) associated with TOB2

01 Sep 2024·Microvascular Research

Circulating miRNA-4701-3p as a predictive biomarker of cardiovascular disease which induces angiogenesis by inhibition of TOB2

Article

Author: Kim, Young-Hak ; Ha, Chang Hoon ; Jeong, I Jin-Yong ; Yoon, Bo Hyun ; Lee, Seung Min ; Pack, Chan-Gi ; Kim, Inki ; Lee, Jin Woo

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction.

01 May 2024·Chemosphere

Multilevel assessment of carbamazepine effects: An integrative approach using zebrafish early-life stages

Article

Author: Camargo, Níchollas Serafim ; Andrade, Thayres Sousa ; Pic-Taylor, Aline ; Grisolia, Cesar Koppe ; Silva, Muriel Lopes da ; Sousa-Moura, Diego ; Domingues, Inês ; Oliveira, Rhaul de ; Lisboa, Carolina Almeida ; Villacis, Rolando André Rios

Carbamazepine (CBZ) is the most commonly used drug in epilepsy treatment, and its metabolites are commonly detected among persistent pharmaceuticals in the aquatic environment. This study aimed to investigate CBZ effects on early-life-stage zebrafish (Danio rerio) (from 2 to 168 hpf) by employing of an integrative approach linking endpoints from molecular to individual level: (i) development; (ii) locomotor activity; (iii) biochemical markers (lactate dehydrogenase, glutathione-S-transferase, acetylcholinesterase and catalase) and (iv) transcriptome analysis using microarray. A 168 h - LC₅₀ of 73.4 mg L^-1 and a 72 h - EC₅₀ of 66.8 mg L^-1 for hatching were calculated while developmental effects (oedemas and tail deformities) were observed at CBZ concentrations above 37.3 mg L^-1. At the biochemical level, AChE activity proved to be the most sensitive parameter, as evidenced by its decrease across all concentrations tested (∼25% maximum reduction, LOEC (lowest observed effect concentration) < 0.6 μg L^-1). Locomotor behaviour seemed to be depressed by CBZ although this effect was only evident at the highest concentration tested (50 mg L^-1). Molecular analysis revealed a dose-dependent effect of CBZ on gene expression. Although only 25 genes were deregulated in organisms exposed to CBZ when compared to controls, both 0.6 and 2812 μg L^-1 treatments impaired gene expression related to development (e.g. crygmxl1, org, klf2a, otos, stx16 and tob2) and the nervous system (e.g. Rtn3, Gdf10, Rtn3), while activated genes were associated with behavioural response (e.g. prlbr and taar). Altogether, our results indicate that environmentally relevant CBZ concentrations might affect biochemical and genetic traits of fish. Thus, the environmental risk of CBZ cannot be neglected, especially in a realistic scenario of constant input of domestic effluents into aquatic systems.

01 Mar 2024·International Journal of Biological Macromolecules

Hsa_circ_0086414/transducer of ERBB2 (TOB2) axis-driven lipid elimination and tumor suppression in clear cell renal cell cancer via perilipin 3

Article

Author: Yuan, Hongwei ; Lu, Feiyi ; Xiao, Wen ; Yu, Tiexi ; Wang, Cheng ; Dong, Wei ; Li, Weiquan ; Meng, Xiangui ; Zhang, Xiaoping ; Yang, Wei

BACKGROUNDRenal cell cancer (RCC) is characterized by abnormal lipid accumulation. However, the specific mechanism by which such lipid deposition is eliminated remains unclear. Circular RNAs (circRNAs) widely regulate various biological processes, but the effect of circRNAs on lipid metabolism in cancers, especially clear cell renal cell carcinoma (ccRCC), remains poorly understood.METHODSThe downregulated circRNA, hsa_circ_0086414, was identified from high-throughput RNA-sequencing data of human ccRCC and pair-matched normal tissues. The target relationship between circRNA_0086414 and miR-661, and the transducer of ERBB2 (TOB2) was predicted using publicly available software programs and verified by luciferase reporter assays. The clinical prognostic value of TOB2 was evaluated by bioinformatic analysis. The expression levels of circRNA_0086414, miR-661, TOB2, and perilipin 3 (PLIN3) were measured by quantitative reverse-transcription polymerase chain reaction or western blot analysis. Cell Counting Kit-8, transwell assays, and xenograft models were employed to assess the biological behaviors of the hsa_circ_0086414/TOB2 axis. Oil Red staining and triglyceride assay was conducted to assess lipid deposition.RESULTSHerein, we identified a downregulated circRNA, hsa_circ_0086414. Functionally, the restored hsa_circ_0086414 inhibited ccRCC proliferation, metastasis, and lipid accumulation in vitro and in vivo. Furthermore, the downregulated TOB2 predicted adverse prognosis and promoted cancer progression and lipid deposition in ccRCC. Mechanically, the binding of hsa_circ_0086414 to miR-661, as a miRNA sponge, upregulates the expression of TOB2, wielding an anti-oncogene effect. Importantly, the restored hsa_circ_0086414/TOB2 axis significantly contributed to the elimination of lipid deposition by inhibiting the lipid metabolism regulator PLIN3 in ccRCC cells.CONCLUSIONSOur data highlight the importance of the hsa_circ_0086414/TOB2/PLIN3 axis as a tumor suppressor and lipid eliminator in ccRCC. The positive modulation of the hsa_circ_0086414/TOB2 axis might lead to the development of novel treatment strategies for ccRCC.

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TOB2

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